Expression patterns and action analysis of genes associated with blood coagulation responses during rat liver regeneration

Abstract

Aim: To study the blood coagulation response after partial hepatectomy (PH) at transcriptional level.

Methods: After PH of rats, the associated genes with blood coagulation were obtained through reference to the databases, and the gene expression changes in rat regenerating liver were analyzed by the Rat Genome 230 2.0 array.

Results: It was found that 107 genes were associated with liver regeneration. The initially and totally expressing gene numbers occurring in initiation phase of liver regeneration (0.5-4 h after PH), G0/G1 transition (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure-function reconstruction (66-168 h after PH) were 44, 11, 58, 7 and 44, 33, 100, 71 respectively, showing that the associated genes were mainly triggered in the forepart and prophase, and worked at different phases. According to their expression similarity, these genes were classified into 5 groups: only up-, predominantly up-, only down-, predominantly down-, up- and down-regulation, involving 44, 8, 36, 13 and 6 genes, respectively, and the total times of their up- and down-regulation expression were 342 and 253, respectively, demonstrating that the number of the up-regulated genes was more than that of the down-regulated genes. Their time relevance was classified into 15 groups, showing that the cellular physiological and biochemical activities were staggered during liver regeneration. According to gene expression patterns, they were classified into 29 types, suggesting that their protein activities were diverse and complex during liver regeneration.

Conclusion: The blood coagulation response is enhanced mainly in the forepart, prophase and anaphase of liver regeneration, in which the response in the forepart, prophase of liver regeneration can prevent the bleeding caused by partial hepatectomy, whereas that in the anaphase contributes to the structure-function reorganization of regenerating liver. In the process, 107 genes associated with liver regeneration play an important role.

Figure 1

Expression frequency, abundance and changes of 107 blood coagulation response-associated genes during rat liver regeneration. Detection data of Rat Genome 230 2.0 array were analyzed and graphed with Microsoft Excel. A: Gene expression frequency. The dots above bias represent the genes up-regulated more than two fold, and total times of up-regulation were 342; those below bias down-regulated more than two fold, and times of down-regulation were 253; and the ones between biases no-sense alteration; B: Gene expression abundance and changes. Seventy-six genes were 2-46 fold up-regulated, and 62 genes 2-10 fold down- regulated.

Figure 2

The initial and total expression profiles of 107 blood coagulation response-associated genes at each time point of liver regeneration. Grey bars: Up-regulated gene; White bars: Down-regulated. Blank bars represent initial expressing genes, in which up-regulated genes were predominant in the forepart, and the down-regulated genes in the prophase and metaphase, whereas there was little initial expression in the anaphase. Dotted bars represent the total expressing genes, in which some genes were up-regulated, and the others down regulated during the whole LR.

Figure 3

Expression similarity and time relevance clusters of 107 blood coagulation response-associated genes during liver regeneration. Detection data of Rat Genome 230 2.0 array were analyzed by H-clustering. Red represents up-regulated genes chiefly associated with promoting blood coagulation; Green represents down-regulated ones mainly associated with inhibiting blood coagulation; Black: No-sense in expression change. The upper and right trees respectively show expression similarity and time series clusters, by which the above genes were classified into 5 and 15 groups separately.

Figure 4

Twenty-nine gene expression patterns of 107 blood coagulation response-associated genes during liver regeneration. Expression patterns were obtained by the analysis of detection data of Rat Genome 230 2.0 array with Microsoft Excel. A-J: 44 up-regulated genes; K-Q: 36 down-regulated genes; R-T: 27 up/down-regulated genes. X-axis represents recovery time after partial hepatectomy (h); Y-axis shows logarithm ratio of the signal values of genes at each time point to control.